P716: GENE EXPRESSION ANALYSIS REVEALS UNIQUE CHARACTERISTICS OF BONE MARROW MESENCHYMAL STROMAL CELLS IN MYELODYSPLASTIC SYNDROME WITH RING SIDEROBLASTS
Authors: Wanshu Chen, Bing Han
Journal: HemaSphere (2023)

Background: Bone marrow mesenchymal stromal cells (BM-MSCs) are critical functional cells in the bone marrow microenvironment, and in Myelodysplastic Syndromes (MDS), BM-MSCs exhibit slow proliferation, increased apoptosis, and reduced hematopoietic support capacity, ultimately leading to abnormal hematopoiesis. MDS-RS is a unique subtype of MDS with immune activation characteristics, which share some similarities with the immune mechanism of aplastic anemia (AA) but have significant differences from some high-risk MDS subtypes, such as MDS-EB. Its genetic and clinical features are likely related to the role of the bone marrow microenvironment. Aims: To explore the gene expression of MDS-RS MSCs and their differences from other MDS subtypes, AA, and healthy control, analyze the effects of differentially expressed genes on upstream and downstream pathways, and describe their role in the pathogenesis of MDS-RS. Methods: MDS patients, AA patients, and healthy individuals diagnosed at the Peking Union Medical College Hospital were recruited, classified according to the 2016 WHO criteria, and their bone marrow blood was extracted for BM-MSCs culture up to P3 for validation. Transcriptional sequencing was performed on collected cells, and differences were analyzed. Results: A total of 11 MDS-RS patients, 3 MDS-SLD/MLD patients, 4 MDS-EB1/2 patients, 4 AA patients, and 5 healthy individuals were recruited. Compared with the healthy control, protein digestion and absorption-related gene expression were upregulated in MDS-RS, including COL11A1 and other genes mainly expressed in mesenchymal-derived tumors. These genes were also upregulated in MDS-SLD/MLD and MDS-EB1/2 but were not significantly higher than in MDS-RS. Compared with AA, the expression of proliferation-promoting genes such as LIF and HBEGF was upregulated in MDS-RS. Compared with MDS-SLD/MLD, DNA replication-related gene expression was slightly lower in MDS-RS, while compared with MDS-EB1/2, the expression of genes in multiple pathways, including DNA replication, DNA repair, cell proliferation, and RNA transport, were down-regulated. Summary/Conclusion: The proliferation ability of BMMSCs from MDS-RS was enhanced compared to the healthy control, with a particularly significant upregulation of tumor-related gene expression originating from the mesenchymal lineage. Despite being a relatively low-risk subtype of MDS, MDS-RS exhibits this type of upregulated gene expression, which may be because while these genes are typically found in mesenchymal-derived tumors, in the case of MDS-RS, MSCs serve as stromal cells rather than malignant cells themselves, and are instead a part of the microenvironment that supports pathological hematopoiesis, thereby enhancing their supportive function. Similar differences were observed when comparing MDS-SLD/MLD and MDS-EB1/2 to healthy control. However, they were not as significant as in MDS-RS, indicating that this process may be unique to MDS-RS.Keywords: Myelodysplastic syndrome, Gene expression, Mesenchymal cells, MDS